Table 4. Kinetic Analysis of Inhibitor Binding to Human Wild-Type and Mutant DHODHsa.
| IC50 (uM) |
|||||
|---|---|---|---|---|---|
| enzyme | 1 | 5 | 10 | 11 | 6 |
| WT 33–396 | 0.21 (0.16–0.26) | >100 | 45 (36–54) | 2.7 (1.8–3.9) | 2.1 (1.5–3.1) |
| L46A | 0.27 (0.17–0.43) | >100 | >100 | >100 | >100 |
| H56A | 1.5 (0.8–3.0) | >100 | 67 (31–100) | 5.3 (2.5–10.9) | 0.9 (0.7–1.1) |
| R136A | 36 (24–48) | >100 | >100 | >100 | >100 |
| L359A | 0.28 (0.22–0.36) | >100 | >100 | >100 | 35 (23–47) |
a
The HsDHODH33–396 construct was used for the mutant analysis. The 95% confidence interval is displayed in parentheses. The data set included three replicates for each inhibitor concentration used in the fit. Experiments were conducted using the direct assay.